Cardiovascular diseases (CVDs), such as high blood pressure, heart attack, stroke, angina pectoris, atherosclerosis, and arteriosclerosis, affect millions of people and are a leading cause of death in the world today. CVDs mainly consist of a progressive narrowing of the arteries that nourish an organ or tissue, e.g., the heart. The narrowing is caused by an excessive buildup of fatty plaque along artery walls. The plaque buildup can lead to aneurism and thrombi, i.e., blood clots, and thrombi in turn can result in thrombosis, heart attack, and stroke.
The key to CVD therapy is early detection and diagnosis so that the proper treatment can be initiated. Accurately identifying the presence, location, and size of a CVD, such as a thrombus or atherosclerotic lesion, within the vascular system is diagnostically significant to establish a proper course of treatment, the need for surgical intervention, and the site of surgery or therapy.
Effective detection and diagnosis of plaque build-up, aneurism, thrombus, and other injuries or disease processes often require the use of imaging techniques to visualize the patient's vascular system. Such imaging techniques include x-ray angiography, computed tomography (CT) and spiral CT angiography, and magnetic resonance imaging (MRI). The use of magnetic resonance angiography (MRA) to diagnose CVDs has become increasingly popular because it is generally perceived to be cost-effective, convenient, and safe. MRA is a non-invasive MRI technique that uses short magnetic pulses to provide three-dimensional (“3D”) images of the arteries and blood vessels that supply blood to the heart and other vital organs.
Contrast agents may be administered during an MRA exam to improve the visualization of the vascular system. A contrast agent is a substance that, when administered to a subject, increases the image contrast (e.g., provides contrast enhancement) between a chosen target, tissue, or organ and the rest of the field of the image (e.g., the remaining areas of the body). “Vascular” contrast agents can improve the visualization of the vascular system by altering the contrast of the vascular system relative to the surrounding tissues, usually by brightening (hyper-intensifying) the vascular system (e.g., the blood).
Injecting a vascular contrast agent into a patient's blood stream provides contrast enhancement to the vascular system image and may allow clinicians to visualize and measure the diameter of blood vessels, including those that are very small. Accurately defining vessel size and diameter is important to CVD diagnosis because the diameter of the vessels indicates the presence of stenoses, characterized by a narrowing of the blood vessels, and aneurisms, characterized by a widening of the vessels. Other types of CVDs may also be indirectly detected through use of a vascular contrast agent during an MRI exam. For example, thrombi and atherosclerotic lesions may be indirectly detected as these displace blood, causing the blood vessels to appear blocked or narrowed in contrast-enhanced images.
Despite the use of vascular contrast agents, the diagnosis of CVDs in the vascular system remains difficult. For example, the physician must seek out dark areas (e.g., areas of negative contrast) of the vascular image, within the bright (e.g., enhanced) vascular system. In addition, the use of vascular contrast agents typically does not allow a physician to distinguish between a vessel that contains a thrombus within the vessel interior and some other type of blockage (e.g., a blockage within the vessel wall).
Another class of contrast agents, referred to herein as “targeted” contrast agents, can function by binding to a particular target that may be present within the vascular system. For example, the targeted agent may bind to a CVD target, e.g., a thrombus, present within a blood vessel. Thus, the targeted agent may enhance the contrast between the target and background tissue and blood by, for example, hyper-intensifying the target relative to background tissue and blood. The use of such targeted agents, however, does not indicate whether the contrast-enhanced target is indeed within a blood vessel, nor does it identify the location or size of the target within the vascular system itself. Thus, a targeted image often lacks important anatomic information required for effective diagnosis and therapy of CVDs.
It would be useful for the clinician to be able to identify accurately the presence, location, and size of CVD targets within the vascular system using a method that is cost-efficient, safe, and convenient. It would be further useful for the clinician to have methods to distinguish a chosen target (e.g., a CVD) and the vascular system one from the other and also from the remaining background tissues in the field of view.